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?-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity.

ABSTRACT: Regardless of their targets and modes of action, subinhibitory concentrations of antibiotics can have an impact on cell physiology and trigger a large variety of cellular responses in different bacterial species. Subinhibitory concentrations of ?-lactam antibiotics cause reactive oxygen species production and induce PolIV-dependent mutagenesis in Escherichia coli. Here we show that subinhibitory concentrations of ?-lactam antibiotics induce the RpoS regulon. RpoS-regulon induction is required for PolIV-dependent mutagenesis because it diminishes the control of DNA-replication fidelity by depleting MutS in E. coli, Vibrio cholerae and Pseudomonas aeruginosa. We also show that in E. coli, the reduction in mismatch-repair activity is mediated by SdsR, the RpoS-controlled small RNA. In summary, we show that mutagenesis induced by subinhibitory concentrations of antibiotics is a genetically controlled process. Because this mutagenesis can generate mutations conferring antibiotic resistance, it should be taken into consideration for the development of more efficient antimicrobial therapeutic strategies.

SUBMITTER: Gutierrez A

PROVIDER: S-EPMC3615471 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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β-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity.

Gutierrez A A Laureti L L Crussard S S Abida H H Rodríguez-Rojas A A Blázquez J J Baharoglu Z Z Mazel D D Darfeuille F F Vogel J J Matic I I

Nature communications 20130101

Regardless of their targets and modes of action, subinhibitory concentrations of antibiotics can have an impact on cell physiology and trigger a large variety of cellular responses in different bacterial species. Subinhibitory concentrations of β-lactam antibiotics cause reactive oxygen species production and induce PolIV-dependent mutagenesis in Escherichia coli. Here we show that subinhibitory concentrations of β-lactam antibiotics induce the RpoS regulon. RpoS-regulon induction is required fo ...[more]

PMID: 23511474

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Project description:The release of antibiotics (AB) into the environment poses several threats for human health due to potential development of AB-resistant natural bacteria. Even though the use of low-dose antibiotics has been promoted in health care and farming, significant amounts of AB are observed in aquatic environments. Knowledge on the impact of AB on natural bacterial communities is missing both in terms of spread and evolution of resistance mechanisms, and of modifications of community composition and productivity. New approaches are required to study the response of microbial communities rather than individual resistance genes. In this study a chemostat-based experiment with 4 coexisting bacterial strains has been performed to mimicking the response of a freshwater bacterial community to the presence of antibiotics in low and high doses. Bacterial abundance rapidly decreased by 75% in the presence of AB, independently of their concentration, and remained constant until the end of the experiment. The bacterial community was mainly dominated by Aeromonas hydrophila and Brevundimonas intermedia while the other two strains, Micrococcus luteus and Rhodococcus sp. never exceed 10%. Interestingly, the bacterial strains, which were isolated at the end of the experiment, were not AB-resistant, while reassembled communities composed of the 4 strains, isolated from treatments under AB stress, significantly raised their performance (growth rate, abundance) in the presence of AB compared to the communities reassembled with strains isolated from the treatment without AB. By investigating the phenotypic adaptations of the communities subjected to the different treatments, we found that the presence of AB significantly increased co-aggregation by 5-6 fold. These results represent the first observation of co-aggregation as a successful strategy of AB resistance based on phenotype in aquatic bacterial communities, and can represent a fundamental step in the understanding of the effects of AB in aquatic ecosystems.

Dataset Information

?-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity.

Publications

β-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity.

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